Increased gelatinase A (MMP-2) and gelatinase B (MMP-9) activities in human brain after focal ischemia.
Matrix metalloproteinases (MMPs) are involved in remodelling extracellular matrix. Gelatinase B (MMP-9) is an inducible 92 kDa MMP expressed by neutrophils, microglia, and endothelial cells. Gelatinase A (MMP-2) is a 72 kDa MMP, constitutively expressed in brain. Elevated MMP activity has been linked to various pathologic conditions, and the therapeutic benefit of MMP inhibitors is under study in a few experimental models. Using gelatin zymography, we have compared activities of these MMPs in infarcted and matched non-infarcted cerebral tissue from eight subjects dying at intervals of less than 2 h to several years after a stroke. Gelatinase B activity was markedly elevated in the infarcted tissue at two days post-infarction, and remained elevated in cases dying months after the event. Increases in gelatinase A activity were subtle at 2-5 days; they were marked and significant in cases dying at 4 months and later. The findings indicate distinct temporal profiles of post-ischemic gelatinase activity in human brain, with earlier but equally persistent elevation in gelatinase B when compared to gelatinase A.
Clark
A W
AW
Department of Pathology, University of Calgary, Canada. awcimp@acs.ucalgary.ca
Krekoski
C A
CA
Bou
S S
SS
Chapman
K R
KR
Edwards
D R
DR
D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000201:enzymology*; D017364:Collagenases / Q000378:metabolism*; D005260:Female; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000378:metabolism*; D008875:Middle Aged; D013997:Time Factors
D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9